p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK
p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK
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DOI：
10.1152/ajpcell.2001.281.1.c123
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发表时间：
2001-07-01
影响因子：
5.5
通讯作者：
Gerthoffer, WT
中科院分区：
文献类型：
--
作者：
Dechert, MA;Holder, JM;Gerthoffer, WT
细胞迁移有助于许多生理过程，并需要细胞骨架的动态变化。这些迁移依赖的细胞骨架变化部分由p21激活蛋白激酶（PAKs）介导。在哺乳动物细胞中至少存在四种密切相关的同种型，PAK 1、PAK 2、PAK 3和PAK 4。在平滑肌细胞中，对PAKs的表达、激活或调节迁移的能力知之甚少。我们的研究表明，在培养的气管平滑肌细胞（TSMCs）中存在三种PAK亚型。此外，我们构建了腺病毒载体编码野生型和催化失活的PAK 1突变体，以研究PAK激活及其在TSMC迁移中的作用。用血小板衍生生长因子（PDGF）刺激TSMC，PAK 1的活性随时间增加。过表达突变PAK 1阻断PDGF诱导的趋化细胞迁移。在过度表达野生型PAK 1的细胞中，p38丝裂原活化蛋白激酶（MAPK）的磷酸化与载体对照相似;然而，PAK 1突变体的过度表达严重降低了p38 MAPK的磷酸化。总的来说，这些结果表明PAK 1在趋化性TSMC迁移中的作用，涉及催化活性，并可能需要在其他途径中向p38 MAPK发出信号。
Cell migration contributes to many physiological processes and requires dynamic changes in the cytoskeleton. These migration-dependent cytoskeletal changes are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammalian cells. In smooth muscle cells, little is known about the expression, activation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (TSMCs). Additionally, we constructed adenoviral vectors encoding wild type and a catalytically inactive PAK1 mutant to investigate PAK activation and its role in TSMC migration. Stimulation of TSMCs with platelet-derived growth factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing wild-type PAK1 was similar to vector controls; however, p38 MAPK phosphorylation was severely reduced by overexpression of the PAK1 mutant. Collectively, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among other pathways.